Disorders of eye movement, particularly abnormal smooth pursuit eye movement, remain one of the few specific neurologic findings in schizophrenia. Despite many studies supporting the presence of eye movement disorders in schizophrenia, their precise nature and how they relate to the etiology and treatment of schizophrenia remain unclear. This project attempts to better define the pathophysiology of eye movement disorders by studying patients with schizophrenia, other neurologic disorders and normal controls utilizing a unique computerized infra-red oculographic recording system which, in contrast to previous studies, allows precise quantitative measurement and analysis of eye movement. We have observed and quantified differences in smooth pursuit performance (smooth pursuit gain) and saccadic intrusions in smooth pursuit between schizophrenic patients and controls. We observed no effect of neuroleptic medication or clinical status on these differences in schizophrenic patients, confirming previous findings. However, in tests of saccadic eye movement, neuroleptic medication reduces the amplitude of predictive saccades. We observed in schizophrenic patients that the performance of smooth pursuit eye movement and the ability to make anticipatory saccades in visually guided saccadic eye tracking tasks is correlated with performance on the Wisconsin Card Sort, a test of frontal lobe function. We also observed that caffeine, a dopamine agonist, improves smooth pursuit performance by reducing saccadic intrusions in normal controls. Since a deficit in dopaminergic neurons arising from frontal cortex has been implicated as a possible mechanism for signs and symptoms in schizophrenia, our proposed course of study includes further comparison of eye movement with other tests of frontal lobe function and further study of the effects of dopamine agonists on eye movement in schizophrenic patients and controls. In addition, since it has been shown that deficits in eye movement may be inherited by unaffected first degree relatives of schizophrenic patients, we plan to study eye movement and other tests of frontal lobe function in family pedigrees in collaboration with the Unit on Molecular Neurogenetics.